A Deeper Look into the Cellular Caves: Caveolins, Cavins and Popdc Proteins in Cardioprotection
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Published:
Feb 20, 2017
Keywords:
aging, cardioprotection, caveolae, caveolin, cavin, GPCR-signaling, ischemia-reperfusion, lipid rafts, microdomain, plasma membrane, popdc, popeye domain-containing, stress-resistance
Main Article Content
Abstract
Cardioprotection is a promising novel therapeutic approach for the treatment of ischemic heart disease (IHD). Various cardioprotective methods such as ischemic, anesthetic and G-protein-coupled-receptor (GPCR) based preconditioning have been shown to be reliant on the presence of unique regions in the sarcolemma termed caveolae. Caveolae compartmentalize and concentrate various classes of signaling molecules involved in stress-resistance, including important mediators of cardioprotection such as receptor tyrosine kinases, GPCRs and their subunits. The unique morphology of caveolae arises from the expression of its coat proteins belonging to those of caveolin, cavin and Popeye domain-containing (Popdc) family of proteins. As outlined in this review, although contributions of caveolins (especially Caveolin-3) in cardioprotection are relatively well-characterized, recent studies indicate that members of the cavins and the Popdc family of proteins are also crucial for sarcolemmal caveolae formation, an important determinant of ischemia-reperfusion (I-R) injury. In this article, we discuss the evidence for the involvement of caveolins, cavins and Popdc family of proteins in cardioprotective signaling and the essential role of caveolae in age-related reduction of cardioprotective signaling. Age-related changes in sarcolemmal makeup as evidenced by down-regulation of caveolins in several types of tissues is linked to decreased stress-resistance, and may help partially explain the refractoriness to protective stimuli in the aging heart. Hence, a greater understanding of the role of caveolae and its coat proteins as briefly outlined here may help facilitate the development of cardioprotective strategies as despite the decades of research, currently there are no effective treatments for limiting I-R injury. Since many of the existing experimental cardioprotective interventions such as the clinically feasible post-conditioning method is reliant on caveolae, methods that enhance or restore caveolae in the aged heart may be a viable therapeutic strategy for the treatment ischemic heart disease.
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1.
Kiessling CJ, Ashton K. A Deeper Look into the Cellular Caves: Caveolins, Cavins and Popdc Proteins in Cardioprotection. BKK Med J [Internet]. 2017 Feb. 20 [cited 2024 Nov. 21];13(1):77. Available from: https://he02.tci-thaijo.org/index.php/bkkmedj/article/view/221803
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2. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124-36.
3. Kidd MW, Reichelt ME, Peart JN, et al. Caveolin and the aged myocardium. FASEB J 2010;4:819-2.
4. Senju Y, Itoh Y, Takano K, et al. Essential role of PACSIN2/ syndapin-II in caveolae membrane sculpting. J Cell Sci 2011;124:2032-40.
5. Morén B, Shah C, Howes MT, et al. EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization. Mol Biol Cell 2012;23:1316-29.
6. nsel PA, Head BP, Patel HH, et al. Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae. Biochem Soc Trans 2005:33;1131-4.
7. acellular Caveolin-3-associated Microdomains in Adult Cardiac Myocytes. J Biol Chem 2005;280:31036-44.
8. Tsutsumi YM, Horikawa YT, Jennings MM, et al. Cardiacspecifc overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning. Circulation 2008;118:1979-88.
9. Patel HH, Head BP, Petersen HN, et al. Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors. Am J Physiol Heart Circ Physiol 2006;291:H344-50.
10. Razani B, Woodman SE, Lisanti MP. Caveolae: From Cell Biology to Animal Physiology. Pharmacol Rev 2002;54:431-67.
11. Lasley, RD. Adenosine Receptors and Membrane Microdomains. Biochim Biophys Act 2012;1808:1284-9.
12. Monaghan-Benson E, Mastick CC, McKeown-Longo PJ. A dual role for caveolin-1 in the regulation of fbronectin matrix assembly by uPAR. J Cell Sci 2008;121:3693-703.
13. Ju H, Venema VJ, Liang H, Harris MB, et al. Bradykinin activates the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway in vascular endothelial cells: localization of JAK/STAT signalling proteins in plasmalemmal caveolae. Biochem J 2000;351(Pt 1):257-64.
14. arcía-Cardeña G, Martasek P, Masters BS, et al. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional signifcance of the nos caveolin binding domain in vivo. J Biol Chem 1997;272:25437-40.
15. Chow AK, Cena J, El-Yazbi AF, et al. Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart. J Mol Cell Cardiol 2007;42:896-901
16. Rothberg KG, Heuser JE, Donzell WC, et al. Caveolin, a protein component of caveolae membrane coats.Cell 1992;68:673-82.
17. Schlegel A, Pestell RG, Lisanti MP. Caveolins in cholesterol trafficking and signal transduction:implications for human disease.Front Biosci 2000;1:D929-37.
18. Drab M, Verkade P, Elger M, et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice.Science 2001;293:2449-52.
19. Park DS, Cohen AW, Frank PG, et al. Caveolin-1 null (-/-) mice show dramatic reductions in life span.Biochemistry 2003;42:15124-31
20. Park DS, Woodman SE, Schubert W, et al. Caveolin-1/3 Double-Knockout Mice Are Viable, but Lack Both Muscle and Non-Muscle Caveolae, and Develop a Severe Cardiomyopathic Phenotype. Am J Pathol 2002;160:2207-17.
21. Kang-Decker N, Cao S, Chatterjee S, et al. Nitric oxide promotes endothelial cell survival signaling through S-nitrosylation and activation of dynamin-2.J Cell Sci 2007;120:492-501.
22. Patel HH, Tsutsumi YM, Head BP, et al. Mechanisms of cardiac protection from ischemia/reperfusion injury: a role
for caveolae and caveolin-1.FASEB 2007;21:1565-74.
23. Jasmin JF, Rengo G, Lymperopoulos A, et al. Caveolin-1 defciency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction. Am J Physiol Heart Circ Physiol 2011;300:H1274-81.
24. Young LH, Ikeda Y, Lefer AM. Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia-reperfusion via nitric oxide mechanism. Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia-reperfusion via nitric oxide mechanism. Am J Physiol Heart Circ Physiol 2001;280:H2489-95.
25. Bucci M, Gratton JP, Rudic RD, et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation.Nat Med 2000;6:1362-7.
26. Shivshankar P, Halade GV, Calhoun C, et al. Caveolin-1 deletion exacerbates cardiac interstitial fbrosis by promoting M2 macrophage activation in mice after myocardial infarction. J Mol Cell Cardiol 2014;76:84-93.
27. Miyasato SK, Loeffler J, Shohet R, et al. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biol 2011;30:318-29.
28. Del Pozo MA, Balasubramanian N, Alderson NB, et al. Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization.Nat Cell Biol 2005;7:901-8.
29. Corrotte M, Almeida PE, Tam C, et al. Caveolae internalization repairs wounded cells and muscle fbers. Elife 2013;2:e00926.
30. Kang-Decker N, Cao S, Chatterjee S, et al. Nitric oxide promotes endothelial cell survival signaling through S-nitrosylation and activation of dynamin-2.J Cell Sci 2007;120:492-501.
31. Bernatchez PN, Sharma A, Kodaman P, et al. Myoferlin is critical for endocytosis in endothelial cells. Am J Physiol Cell Physiol 2009;297:C484-92.
32. Cheng JP, Mendoza-Topaz C, Howard G, et al. Caveolae protect endothelial cells from membrane rupture during increased cardiac output.J Cell Biol 2015;211:53-61.
33. Ortiz-Pérez JT, Lee DC, Meyers SN, et al. Determinants of myocardial salvage during acute myocardial infarction: evaluation with a combined angiographic and CMR myocardial salvage index.JACC Cardiovasc Imaging 2010;3:491-500.
34. Lund GK, Stork A, Muellerleile K, et al. Prediction of left ventricular remodeling and analysis of infarct resorption
in patients with reperfused myocardial infarcts by using contrastenhanced MR imaging.Radiology 2007;245:95-102.
35. Lund GK, Stork A, Muellerleile K, et al. Prediction of left ventricular remodeling and analysis of infarct resorption
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